These studies suggest that the leukemogenic process in AKR mice selectively affects subpopulations of PHA and Con A responsive lymphocytes in the periphery and in the thymus, but that there is no generalized major deficit of T cells before leukemia development. These differential changes in spleen and thymus cell reactivity to mitogens may reflect a differential susceptibility of PHA and Con A responsive cells to infection by murine leukemia viruses.